OSTEOARTHRITIS AND AGING

骨关节炎与衰老

• 批准号: 2333506
• 负责人: J D TOBIN
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2333506
• 关键词: African American; aging; body composition; bone imaging /visualization /scanning; cardiovascular disorder epidemiology; caucasian American; clinical research; disease /disorder proneness /risk; gender difference; genetic markers; genetic polymorphism; hand; hormone therapy; human middle age (35-64); human old age (65+); human subject; knee; longitudinal human study; orthopedics; osteoarthritis; postmenopause; questionnaires; restriction fragment length polymorphism; tobacco abuse; women's health

Osteoarthritis (OA) is the most common form of arthritis in the elderly, and is a major cause of activity limitation, physical disability and health services utilization in the elderly. As part of the ongoing studies of OA in the Baltimore Longitudinal Study of Aging (BLSA), in order to test the hypothesis that genetic markers may be implicated in the expression of OA, especially generalized (polyarticular) OA, we have examined the association between alleles of the polymorphic human aggrecan gene (at least 11 alleles identified) and bilateral hand and knee OA in 74 Caucasian men aged 60 and over. DNA grown from fibroblast samples obtained from these subjects, who had bilateral hand and knee x-rays, has been analyzed by PCR and/or Southern analysis for the presence of alleles of the human aggrecan gene. After adjustment for age and body mass index (BMI), it appears that the presence of allele#5 is associated with increased odds of bilateral hand OA (Odds ratio [OR] 5.3, p=0.007), but not with bilateral knee OA, which would be the first association between a human aggrecan gene polymorphism and OA. We are currently analyzing several more samples in women as well. We also examined the history of knee surgery with knee OA in 545 Caucasian men and 350 Caucasian women. 36 subjects had knee surgery prior to the x-ray. Multivariate models, adjusting for age, BMI, gender and smoking status at the time of x-ray, demonstrated increased odds ratios (OR[95%CI]) of knee OA as measured on the Kellgren-Lawrence (KL) scale (108.4 [12.8, 916.8]), the Osteophyte scale (15.4 [5.9, 39.8]), and Joint space narrowing (JSN) (12.5 [5.5, 28.3]). Knee surgery is significantly associated with knee OA, although the indication for the surgery may be a contributing or confounding factor. We also examined factors predictive of total knee replacement surgery (TKR) in 177 Caucasians (126 men and 51 women), who had definite radiographic knee OA, and completed symptoms questionnaires at the time of x-ray. 11 of the subjects had a TKR 1-8 years following the knee x-ray. Multivariate models, adjusting for age, BMI, gender and smoking status at the time of the x-ray, demonstrated increased odds of TKR among subjects with the following: Pain (14.0 [2.8, 68.9]), KL grades 2-4 (23.4 [4,4, 114.2]), and JSN (19.5 [2.3, 162.0]), and Sclerosis (19.2 [4.4, 82.8). Moderate-to-severe knee OA, joint space narrowing, and subchondral sclerosis, with concurrent knee pain, are all predictive of total knee replacement. In addition to the above completed work, since January 1996, we have been collecting knee radiographs on all BLSA subjects aged 40 and over, in order to add to our limited collection of longitudinal knee x-ray data, and to provide more cross-sectional and baseline data on African American participants in the BLSA.

骨关节炎（OA）是老年人最常见的关节炎形式， 并且是活动受限、身体残疾和健康的主要原因 老年人的服务利用。作为正在进行的OA研究的一部分， 在巴尔的摩老龄化纵向研究（BLSA）中，为了测试 假设遗传标记可能与以下基因的表达有关： OA，特别是全身性（多关节）OA，我们检查了 多态性人聚集蛋白聚糖基因的等位基因之间的关联（at 在74例高加索人中， 60岁及以上的男性。从成纤维细胞样品中生长的DNA， 这些受试者接受了双手和膝盖的X光检查， 通过PCR和/或Southern分析来分析以下基因的等位基因的存在 人类聚集蛋白聚糖基因 调整年龄和体重指数后 (BMI)，似乎等位基因#5的存在与 双侧手部OA的几率增加（比值比[OR] 5.3，p=0.007），但 与双侧膝关节OA，这将是第一个之间的关联， 人聚集蛋白聚糖基因多态性与骨关节炎我们目前正在分析 在女性身上也有更多的样本我们还研究了 545例白人男性和350例白人膝关节OA患者膝关节手术 妇女36例受试者在X线检查前接受了膝关节手术。多元 模型，调整年龄，BMI，性别和吸烟状态时， X线检查显示膝关节OA的比值比（OR[95%CI]）增加， 根据Kelly-Lawrence（KL）量表（108.4 [12.8，916.8]）测量， 骨赘评分（15.4 [5.9，39.8]）和关节间隙狭窄（JSN）（12.5 [5.5，28.3]）。膝关节手术与膝关节OA显著相关， 尽管手术的适应症可能是一个促成因素， 混杂因素我们还研究了全膝关节置换术后 177名白人（126名男性和51名女性）接受了置换手术（TKR）， 有明确的影像学膝关节OA，并完成症状 X光检查时的问卷调查。11例受试者的TKR为1-8 膝盖X光检查后的几年多变量模型，根据年龄调整， X光检查时的BMI、性别和吸烟状况， 在具有以下症状的受试者中，TKR的几率增加：疼痛（14.0 [2.8， 68.9]）、KL 2-4级（23.4 [4，4，114.2]）和JSN（19.5 [2.3，162.0]），以及 硬化（19.2 [4.4，82.8）。中重度膝关节OA，关节间隙 狭窄和软骨下硬化，并发膝关节疼痛， 预测全膝关节置换术。除上述已完成的 自1996年1月以来，我们一直在收集膝关节X光片， 所有40岁及以上的BLSA受试者，以增加我们有限的 收集纵向膝关节X线数据，并提供更多 非裔美国人参与者的横截面和基线数据， BLSA。